Isaacs' syndrome as the initial presentation of malignant thymoma and associated with double-positive voltage-gated potassium channel complex antibodies, a case report.

BACKGROUND: Isaacs' syndrome is a peripheral nerve hyperexcitability (PNH) syndrome due to peripheral motor nerve instability. Acquired Isaacs' syndrome is recognized as a paraneoplastic autoimmune disease with possible pathogenic voltage-gated potassium channel (VGKC) complex antibodies. However, the longitudinal correlation between clinical symptoms, VGKC antibodies level, and drug response is still unclear. CASE PRESENTATION: A 45-year-old man had progressive four limbs soreness, muscle twitching, cramps, and pain 4 months before admission. Electromyography (EMG) studies showed myokymic discharges, neuromyotonia, and an incremental response in the high-rate (50 Hz) repetitive nerve stimulation (RNS) test. Isaacs' syndrome was diagnosed based on clinical presentations and EMG reports. Serum studies showed positive VGKC complex antibodies, including leucine-rich glioma-inactivated 1 (LGI1) and contactin-associated protein-like 2 (CASPR2) antibodies. The acetylcholine receptor antibody was negative. Whole-body computed tomography (CT) and positron emission tomography revealed a mediastinal tumor with the great vessels encasement, right pleura, and diaphragm seeding. Biopsy confirmed a World Health Organization type B2 thymoma, with Masaoka stage IVa. His symptoms gradually improved and both LGI1 and CASPR2 antibodies titer became undetectable after concurrent chemoradiotherapy (CCRT) and high dose steroid treatment. However, his Isaacs' syndrome recurred after the steroid was reduced 5 months later. Follow-up chest CT showed probable thymoma progression. LGI1 antibody turned positive again while CASPR2 antibody remained undetectable. CONCLUSIONS: Our patient demonstrates that Isaacs' syndrome could be the initial and only neuromuscular manifestation of malignant thymoma. His Isaacs' syndrome is correlated well with the LGI1 antibody level. With an unresectable thymoma, long-term immunosuppressant therapy may be necessary for the management of Isaacs' syndrome in addition to CCRT for thymoma.

A "coughed up" tissue diagnosed as type A thymoma in an 80-year-old man: A case report.

RATIONALE: Thymoma is the most common primary tumor in the anterior mediastinum. All major subtypes of thymoma can be clinically aggressive. However, type A thymoma is usually benign and rarely invasive, let alone invasive to the trachea. There are no published reports of thymoma diagnosed in a "coughed up' tissue". Here, we report an 80-year-old man who coughed up a piece of tissue which was histopathologically diagnosed as type A thymoma. PATIENT CONCERNS: An 80-year-old man who had a history of thymoma for 8 years was admitted in our hospital with his severe cough and dyspnea and his "coughed up" something. He felt much better after coughing up the piece of tissue. He saved the tissue and sent it to the pathology department. DIAGNOSES: The clinical diagnosis was lung cancer. But the final pathological diagnosis was type A thymoma. INTERVENTIONS: The patient refused to get chemotherapy, or surgery, and only would like to get the traditional Chinese medicine. OUTCOMES: The patient is stable for 19 months after he coughed up some of the tumor tissue. LESSONS: The type A thymoma could be slowly aggressive. If left untreated, it would also invade into the trachea. When treat a patient with history of even a benign tumor, we should always bear the rare possibility in mind to avoid misdiagnosis. For an elderly patient, a "wait and see" policy may be acceptable.

Is thymomectomy equivalent to complete thymectomy in non-myasthenic patients with early-stage thymoma?

A best evidence topic in thoracic surgery was written according to a structured protocol. The question addressed is whether thymomectomy can be equivalent to thymectomy for non-myasthenic early-stage thymoma in terms of recurrence and survival. Ten papers were chosen to answer the question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers were tabulated. All studies included in this analysis are retrospective; most of them are small and from single-institution experiences, and only 3 used propensity-matched analysis to minimize the patients' selection bias. The choice of performing thymectomy or thymomectomy was based on surgeons' preference rather than on a standardized surgical approach. Most papers found that thymectomy was equivalent to thymomectomy in terms of outcomes, but these results could be affected by the intergroup differences in terms of follow-up length, administration of induction or adjuvant therapy, histological subtypes distribution and tumour size. Conversely, the studies of the Japanese Association for Research on the Thymus and the Chinese Alliance for Research in Thymoma found a higher rate of local recurrence in the thymomectomy group than in the thymectomy group. The National Comprehensive Cancer Network, National Cancer Institute and International Thymic Malignancy Interest Group recommend complete thymectomy in non-myasthenic patients with early thymoma; therefore, the identified studies in this review are not strong enough to change this recommendation.

Cytoreductive Pleurectomy and Intrathoracic Chemohyperthermia for Pleural Relapse of Thymomas.

Several surgical procedures, from debulking to extrapleural pneumonectomy, may be applied for stage IVa Masaoka thymomas, but their efficiency is still controversial. Case studies have favored R0 resection as the cornerstone of multimodal therapy for locoregional metastatic extension. This report describes a standardized procedure combining a cytoreductive surgical procedure and intrathoracic chemohyperthermia on a 46-year-old patient presenting with B2 thymoma and synchronous unilateral pleural metastasis.

Peritoneal recurrence of thymoma treated by surgery and hyperthermic intraperitoneal chemotherapy.

Thymomas are rare (1,5 cases/million) and typically occur in adults with a median age of 50 years old. Thymomas are indolent with a 10-year overall survival for resected stage II thymomas of 70%. Late relapses occur in 20% of the cases, and distant metastasis from thymoma is rare. Peritoneal recurrence of thymoma treated with surgery associated with hyperthermic intraperitoneal chemotherapy (HIPEC) has not been described in the literature. This report manages peritoneal recurrence of thymoma with HIPEC, suggesting that aggressive therapies may decrease the risk of recurrence.

Intra-Thoracic Chemo-Hyperthermia for pleural recurrence of thymoma.

BACKGROUND: Pleural recurrences are a hallmark of thymomas, and represent a challenge for multidisciplinary management. The purpose of this study was to assess the feasibility and the results in terms of morbidity, mortality and survival rates, of Intra-Thoracic Chemo-Hyperthermia (ITCH) for the treatment of pleural recurrences of thymomas. METHODS: Retrospective analysis of 19 consecutives patients between 1997 and 2015 treated by surgical cytoreduction (pleurectomy) followed by ITCH with 25mg/m2 of mitomycin, and 50mg/m2 of Cisplatin. RESULTS: There were 8 men and 11 women with a median age of 44 years. ITCH was combined with pleurectomy alone in 4 (22%) patients, pleurectomy and wedge resections in 14 (74%) patients; 1 (5%) patient had a pleuropneumonectomy. There were no perioperative deaths, and 5 patients (26%) presented with postoperative complication, including 3 (16%) cases related to chemotherapy (one case of reversible grade 2 bone marrow aplasia, and 2 cases of reversible, acute kidney failure). The median length of stay in intensive care unit and hospital were 1day and 10days, respectively. After a median follow-up period of 39 months (range 10-127 months), median disease-free survival was 42 months. Five patients (26%) died during follow-up. CONCLUSIONS: Our data indicate that ITCH is a feasible option for selected patients with pleural recurrence of thymomas. ITCH clearly provides long local control, without major safety issues, and prolonged survival may be achieved in selected patients. This therapeutic option should be discussed at a multidisciplinary tumor board.

Hypothermia in VGKC antibody-associated limbic encephalitis.

Voltage-gated potassium channel antibody (VGKC-Ab)-associated limbic encephalitis (LE) is a recently described syndrome that broadens the spectrum of immunotherapy-responsive central nervous system disorders. Limbic encephalitis is typically characterised by a sub-acute onset of disorientation, amnesia and seizures, but the clinical spectrum is not yet fully defined and the syndrome could be under-diagnosed. We here describe the clinical profile of four patients with VGKC-Ab-associated LE who had intermittent, episodic hypothermia. One of the patients also described a prodrome of severe neuropathic pain preceding the development of limbic symptoms. Both of these novel symptoms responded well to immunosuppressive therapy, with concurrent amelioration of amnesia/seizures.